This review explains that adding fatty‑acid‑like tags (acylation) to proteins can change how cancer cells process energy, and that many types of these tags (like palmitoylation) are linked to tumor growth, suggesting they could become drug targets in the future.

With the development of high-resolution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), various modifications resulting from the reactivity of acyl-CoA intermediates with protein residues have been identified. Acylation modifications, a diverse type of post-translational modifications (PTMs), play pivotal roles in regulating protein functions and are critically involved in tumor metabolic reprogramming. These modifications exhibit significant regulatory effects in various cancers, and their dysregulation is closely associated with malignant tumor progression. In this review, we summarize existing evidence and describe how different types of acylation modifications, including succinylation, crotonylation, lactylation, palmitoylation, and β-hydroxybutyrylation, regulate protein functions and signaling pathways, thereby influencing tumor metabolism reprogramming. Future research into the regulatory functions of acylation modifications and their roles in tumor metabolism will help elucidate the molecular mechanisms of metabolic reprogramming and provide potential targets for developing novel diagnostic and therapeutic strategies for cancer.